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Enhanced Direct Major Histocompatibility Complex Class I Self-Antigen Presentation Induced by Chlamydia Infection

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https://ir.library.oregonstate.edu/concern/articles/000001651

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Abstract
  • The direct major histocompatibility complex (MHC) class I antigen presentation pathway ensures intracellular peptides are displayed at the cellular surface for recognition of infected or transformed cells by CD8⁺ cytotoxic T lymphocytes. Chlamydia spp. are obligate intracellular bacteria and, as such, should be targeted by CD8⁺ T cells. It is likely that Chlamydia spp. have evolved mechanisms to avoid the CD8⁺ killer T cell responses by interfering with MHC class I antigen presentation. Using a model system of self-peptide presentation which allows for posttranslational control of the model protein's stability, we tested the ability of various Chlamydia species to alter direct MHC class I antigen presentation. Infection of the JY lymphoblastoid cell line limited the accumulation of a model host protein and increased presentation of the model-protein-derived peptides. Enhanced self-peptide presentation was detected only when presentation was restricted to defective ribosomal products, or DRiPs, and total MHC class I levels remained unaltered. Skewed antigen presentation was dependent on a bacterial synthesized component, as evidenced by reversal of the observed phenotype upon preventing bacterial transcription, translation, and the inhibition of bacterial lipooligosaccharide synthesis. These data suggest that Chlamydia spp. have evolved to alter the host antigen presentation machinery to favor presentation of defective and rapidly degraded forms of self-antigen, possibly as a mechanism to diminish the presentation of peptides derived from bacterial proteins.
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  • Cram, E. D., Simmons, R. S., Palmer, A. L., Hildebrand, W. H., Rockey, D.D., & Dolan, B. P. (2016). Enhanced direct major histocompatibility complex class I self-antigen presentation induced by Chlamydia infection. Infection and Immunity, 84(2), 480 –490. doi:10.1128/IAI.01254-15
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  • 84
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  • 2
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  • HHS | National Institutes of Health (NIH) provided funding to Brian P. Dolan under grant number K22AI089861. HHS | National Institutes of Health (NIH) provided funding to Brian P. Dolan under grant number R56AI112588.
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